It is now well-recognized that characteristic changes in T-cell subsets occur during infection with human immunodeficiency virus (HIV). However, these T cell changes have been characterized primarily in adults with HIV infection, with little available data in infected children. There is difficulty in extrapolating findings obtained in adults to children due to immunologic factors peculiar to the pediatric population. These include the age-dependent normal physiologic variation in lymphocyte number and phenotype and the unique P-O (indeterminant infection) classification, which has no counterpart for comparison in adults. In addition, there are reasons to believe that the immunopathogenesis of HIV infection may differ in children versus adults. Perinatal infection with HIV results in exposure of a naive immune system on HIV, with generally deficient antiviral cellular immunity, and the potential for impact on lymphocyte post-thymic differentiation. The goal of this proposal is to identify cell surface phenotypes that can be used as surrogate markers for the efficacy of antiviral therapy or the progression of disease in HIV-infected children. The study is designed to test the hypothesis that expression of cell surface activation and differentiation antigens on CD4 and Cd8 cells directly reflects the effects of HIV on the developing immune system of infected children. The specific aims will be 1) to characterize changes in post-thymic lymphocyte differentiation resulting from perinatal infection with HIV, 2) to determine the extent of lymphocyte activation, particularly of CD8 cells, occurring in response to HIV infection, and 3) to determine the ability of antiviral therapy to reverse these pathologic changes reflected in the cell phenotype. Alteration in the expression of specific differentiation and activation antigens will be measured by 3-color immunofluorescence and laser flow cytometry. Data obtained in HIV-infected children will be compared to that of age-matched healthy pediatric controls. Studies of cell phenotype in the pediatric population are vital not only to understanding the immunopathogenesis of HIV infection children but to identifying surrogate markers essential to assessment of therapeutic interventions.